The heterogeneity of the COVID-19 clinical manifestation may be associated with the characteristics of the genome of both humans and the virus. A combination of allelic variants of genes associated with viral life cycle can determine susceptibility to SARS-CoV-2 infection. Allelic variants in genes ACE1, ACE2, TMPRSS2, IL6, SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, and XCR1 can determine the severity of COVID-19. Analysis of the genomes of COVID-19 patients with different clinical course and development on their basis of model for stratification of people according to the degree of susceptibility and severity of manifestation will make it possible to develop a personalized approach for the prevention and treatment of COVID-19.